tbuckley/cabot-search huggingface dataset:
Real-world response endpoints in patients with mNSCLC treated with chemotherapy across real-world datasets.
Authors: Brittany Avin McKelvey, Elizabeth Garrett-Mayer, Andrew J. Belli, Thomas D. Brown, Jessica Dow, Janet L. Espirito, Paul Kluetz, Xinran Ma, Andrea McCracken, Pallavi Shruti Mishra-Kalyani, Yanina Natanzon, Danielle Potter, Donna Rivera, Hillary Stires, Mark Stewart, Jeff Allen
Journal: Journal of Clinical Oncology (2023)

6595 Background: Response Evaluation Criteria in Solid Tumors (RECIST) based response rate (RR) is used for efficacy evaluation in clinical trials and relies on imaging data collected at specified timepoints for uniform assessment. In routine clinical practice, the method and timing of response assessment can vary, and imaging data from electronic health records (EHR) and other real world (rw) sources may not be available, making RECIST-based assessment of rw-response rate (rwRR) using rw data (RWD) challenging. Friends of Cancer Research formed a multi-stakeholder partnership to assess available data attributes to measure response across RWD sources to inform development of a consistent method for measurement. Methods: The study included seven EHR data partners who identified and analyzed a cohort of 1,380 patients (pts) with metastatic non-small cell lung cancer (mNSCLC) treated with first-line platinum doublet chemotherapy, following a common protocol and statistical analysis plan. The availability and frequency of data components to assess response including raw images, radiology imaging reports, and clinician response assessments from provider notes were assessed. Response endpoints measured included rwRR, rw-duration of response (rwDOR), and the association of rwR with rw-overall survival (rwOS), rw-time to treatment discontinuation (rwTTD), and rw-time to next treatment (rwTTNT). Results: The availability of data components varied across RWD sources (Table). Images were not widely accessible, thus response was analyzed using clinician response assessments (median proportion of pts evaluable, 77.5%). Of these assessments, the majority relied on imaging interpretation. The median rwRR was 46% with a median rwDOR of 119 days. The table provides median rwTTD, rwTTNT, and rwOS across data sources. Conclusions: The rwRR among pts with mNSCLC calculated using the clinician assessment was relatively consistent across all RWD sources, with consistent trends in time to event endpoints. While variability in the availability of data components to assess response was observed, the demonstrated feasibility of response endpoints based on clinician assessment suggests further exploration may inform drug effectiveness evaluation with RWD. [Table: see text]
Differential efficacy of antidepressants in the treatment of hormone mediated depression in patients with ER+ breast cancer.
Authors: Martha M Kato, Constanza Martinez, Maria Currier, Muni B. Rubens
Journal: Journal of Clinical Oncology (2023)

e24181 Background: Tamoxifen (TAM) and aromatase inhibitors (AI) are associated with a high side-effect burden including depression and cognitive deficits which compromise quality of life and adherence to treatment. The aims of the study were to determine the efficacy of antidepressants (AD) with hormone mediated depression in ER+ breast cancer patients and to determine if any clinical variables predicted successful AD treatment response. Methods: A retrospective chart review of consecutive referrals to psycho-oncology of breast cancer patients on TAM or AI with new onset depression was conducted. Demographic variables, cancer stage and treatment, hormonal treatment, psychiatric history and AD treatment were collected. Assessments for depression, anxiety and cognitive disorders included clinical interviews, patient-rated scales [Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI)] and a clinician-rated scale [Montreal Cognitive Assessment (MoCA)]. These measures were done at baseline (before starting an AD) and follow-up to determine AD treatment response. Successful AD treatment is defined as ≥50% reduction in baseline BDI score, while remission of depression is defined as a BDI score &lt; 8. Statistical analysis comparing clinical variables between AD responders and non-responders included Fischer’s exact test or chi-square, one-way ANOVA, t-test, and binary logistic regression to determine which variables predicted successful AD treatment response. Results: A sample of 40 ER+ breast cancer patients (mean age 55 years; 39 females, 1 male; 26 Hispanic, 14 non-Hispanic) included 18 on TAM and 22 on AI. AD included venlafaxine (N = 18), escitalopram (N = 9), bupropion (N = 4), mirtazapine (N = 4), sertraline (N = 3) and duloxetine (N = 2). Over 72% (29/40) of patients successfully responded to AD with a complete depression remission rate of 50% (20/40). Venlafaxine at a mean dose of 150 mg was significantly more effective (p = .013) in treating hormone-mediated depression when compared to selective serotonin reuptake inhibitors (SSRIs) and other AD (bupropion, mirtazapine). Specifically, 94% (17/18) of patients on venlafaxine successfully responded. Other variables such as cancer stage and treatment, demographics, psychiatric history, and specific hormonal therapy did not predict AD treatment response. Conclusions: Venlafaxine 150 mg daily yielded significantly higher rates of AD response and complete remission of depression in ER+ breast cancer patients with TAM-induced and AI-induced major depression. Venlafaxine was significantly more effective than SSRIs and atypical AD. This high rate of response is likely due to dual serotonin and norepinephrine reuptake inhibition achieved at 150 mg dosing. Venlafaxine can be safely administered with TAM.
The changing landscape of small-cell lung cancer.
Authors: Giordano Fabricio Cittolin Santos, Brendan Knapp, Bharath Ganesh, Feng Gao, Tom Stinchcombe, Ramaswamy Govindan, Daniel Morgensztern
Journal: Journal of Clinical Oncology (2023)

e20634 Background: Small-cell lung cancer (SCLC) is an aggressive histologic subtype of lung cancer with distinct biology and clinical course. The aim of this study is to investigate the trends in demographics and outcomes. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) database to assess the incidence, demographics, and survival for SCLC using SEER 8 (8 registries), which include data from 1975 to 2019. The pattern of metastases was evaluated using SEER 17 from 2010 to 2019. Jointpoint analysis was used to calculate the trends in annual percentage change according to year of diagnosis. Results: There were 530,198 patients with lung cancer, including 73,362 (13.8%) patients with SCLC in the SEER 8. The percentage of SCLC among all lung tumors progressively increased from 13.3% in 1975 to a peak of 17.5% in 1986, followed by steadily decrease since 1990, reaching 11.1% in 2019. The incidence per 100,000 population increased from 9.5 in 1975 to 15.3 in 1986 followed by a gradual decline to 6.5 in 2019. Among patients with SCLC included in SEER 8, demographic changes from 1975-1979 to 2015-2019 included increased median age at diagnosis from 63 years to 69 and increased percentage of women from 31.4% to 51.2%. The percentage of patients with stage IV increased from 56.9% to 63.8% from 1995-1999 to 2000-2004, and to 69.5% in 2010-2014 without further increase. Among the 55,035 patients with SCLC in SEER 17 from 2010 to 2019, the most common sites of metastasis at diagnosis were mediastinal lymph nodes (69.9%) liver (30.5%), bone (22.8%), and brain (15.8%). The median, 1-year, and 5-year overall survival increased from 6 months, 23%, and 3.6% respectively in 1975-1979 to 7 months, 30.8%, and 6.8% respectively in 2010-2019 (P &lt; 001). Conclusions: The incidence of SCLC in the United States reached a peak in 1985 to 1989 followed by a gradual decline. Demographic changes included an increased median age at diagnosis and the percentage of women, which surpassed men in the last study period. There was also an increase in the percentage of stage IV. The improvement in 5-year OS has been statistically significant but clinically modest.
The association of HLA-DR and PD-L1 expression with clinical characteristics in prostate adenocarcinoma.
Authors: Daniel Tuerff, Daniel J. Muller, Coen Johannes Gerardus Lap, Shanshan Liu, Guoqing Diao, Martha Antonio, Victor Nava, Maneesh Rajiv Jain
Journal: Journal of Clinical Oncology (2023)

e17017 Background: Prostate adenocarcinoma is the second most commonly occurring cancer in men, yet therapeutic progress in the past decade has stalled. Immune checkpoint inhibitors (ICI) are being successfully used for the treatment of multiple types of cancers and remain an appealing treatment option for patients with prostate adenocarcinoma. Unfortunately, only a small group of patients with prostate cancer appear to benefit from treatment with ICI. Both HLA-DR and PD-L1 have been identified as predictors of response to ICI in other malignancies. We investigated the prevalence of HLA-DR and PD-L1 expression in prostate cancer, and if there is a correlation with clinical characteristics. Methods: For this retrospective cohort study, 40 patients were randomly selected from a database of patients with prostate cancer seen at the Washington DC VA Medical Center between 2000 and 2022; 19 patients (47.5%) with metastatic disease at presentation and 21 patients (52.5%) presenting without metastatic disease. Clinical information was collected and included age at diagnosis, ethnicity, PSA at diagnosis, total Gleason score, and AJCC stage. Tissue samples of the primary tumors were retrieved and immunohistochemistry was performed for HLA-DR and PD-L1. Staining was independently scored by two experienced pathologists who were blinded to clinical information. Results: HLA-DR was found to be expressed in 14 patients (35%) with prostate cancer, whereas PD-L1 positivity was identified in 18 patients (45%). HLA-DR expression was not associated with metastatic disease, PSA at diagnosis, Gleason score, or AJCC stage ( p = 0.816, p = 0.314, p = 0.920, p = 0.458, respectively). In contrast, PD-L1 positivity was significantly associated with metastatic disease ( p = 0.028), a higher PSA at diagnosis ( p = 0.041), Gleason score ( p = 0.026), as well as AJCC stage ( p = 0.0438). No correlation was observed between HLA-DR positivity and positivity for PD-L1 ( p = 0.641). Conclusions: Both HLA-DR and PD-L1 are found to be expressed in tumor tissues of patients with prostate adenocarcinoma. Although HLA-DR expression was not associated with clinical characteristics, we did observe an association between PD-L1 positivity and advanced disease. This observation would be consistent with prior studies that have reported that PD-L1 expression in prostate cancer is correlated with clinic-pathologic features such as advanced stage of disease, castration resistance and poor overall survival. More studies are necessary to evaluate if PD-L1 could serve as prognostic or predictive biomarker in prostate adenocarcinoma.
<i>BRCA1</i> and <i>RAD51</i> methylation impact on outcome in patients with advanced ovarian cancer: A PAOLA-1 ancillary study.
Authors: Helene Blons, Justine Abdelli, Valerie Taly, Claire Mulot, Pierre Laurent Puig, Benoit You, Philipp Harter, Domenica Lorusso, Yolanda Garcia, Christian Schauer, Sakari Hietanen, Nicoletta Colombo, Ignace Vergote, Hiroaki Kobayashi, Thibault De La Motte Rouge, Paul Buderath, Sabrina Chiara Cecere, Guillaume Bataillon, Eric Pujade-Lauraine, Isabelle Laure Ray-Coquard
Journal: Journal of Clinical Oncology (2023)

5559 Background: The PAOLA-1/ENGOT-ov25 trial showed that adding olaparib (ola) to maintenance bevacizumab (bev) after first-line therapy led to a progression-free and overall survival benefit in advanced ovarian high-grade carcinoma (AOC) patients with homologous recombination deficiency (HRD) (Myriad MyChoice R Genomic Instability Score) or BRCA1/2 mutations (BRCAmut). Here, we address the impact of BRCA1 and RAD51C epimutations to improve our understanding of GIS beyond BRCAmut. Methods: BRCA1 and RAD51C methylation analysis was assessed and quantified in pre-treatment biopsies (66%), after neoadjuvant chemotherapy (NACT) (20%) or unknown (14%) from bisulfite converted DNAs using fluorescent methylation specific PCR and methylation specific droplet digital PCR (ddPCR). Methylation status was correlated to clinical data, BRCA1/2 mutations, GIS and HRD scores, PFS (PFS1, PFS2) and OS. R (r-project.org) was used for statistical analysis. Results: Among the 537 patients randomized to maintenance ola + bev and 269 to placebo (pbo) + bev, 348 and 171 were available for methylation analysis. Their baseline molecular and clinical characteristics were well balanced with those of the entire cohort. Promoter methylation was identified in 67 (12.9%) samples for BRCA1 and 25 (4.8%) for RAD51C (4 were methylated on both genes). Methylation and BRCAmut were mutually exclusive except for 3 samples. Mean GIS scores were 62.5 [59.6-65.5]; 59.4 [57.2-61.5]; 54.2 [50.5-57.8]; 23.4 [21.6-25.2] for BRCA1 or RAD51C methylated ( met-tumors), BRCAmut, non-mut/non-met HRD+ ( b-/m-HRD+) and HRP (proficient) tumors respectively. Among met-tumors 92% (66/72) were GIS positive (&gt;42). The mean GIS score of Met-tumors were significantly higher than that of b-/m- HRD+ samples (p=0,009). Benefit of adding ola maintenance to bev was in a similar between patients with met AOC and those with b-/m- HRD+ tumors ( table). Conclusions: Methylated BRCA1/RAD51 tumors are HRD+ and provide to ovarian cancer patients a similar clinical benefit of ola+bev as patients with b-/m- HRD+ tumors. Methylation assessment represents a rapid and cost effective tool; which coupled with BRCA1-2 somatic testing allows the identification of the majority (81%) of HRD+ AOC. Clinical trial information: NCT02477644 . [Table: see text]
Pegylated liposomal doxorubicin and carboplatin versus paclitaxel and carboplatin as first-line treatment for Chinese patients with ovarian cancer: A multi-center, randomized, open-label trial.
Authors: Yuanming Shen, Beihua Kong, Bairong Xia, Fei Wang, Rutie Yin, Qingshui Li, Ying Yue, Shan Kang, Liping He, Ke Wang, Yuanguang Meng, Shixuan Wang, Pengpeng Qu, Xianghua Huang, Ruixia Guo, Ping Yan, Mei Pan, Ge Lou, Wenjun Cheng, Xing Xie
Journal: Journal of Clinical Oncology (2023)

5556 Background: Paclitaxel combined with carboplatin is a standard first-line chemotherapy regimen for ovarian cancer. This study was designed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) plus carboplatin (CD) compared with paclitaxel plus carboplatin (CP) as first-line treatment for epithelial ovarian cancer (EOC). Methods: Patients with stage IC to IV EOC, fallopian tube cancer, or primary peritoneal cancer were eligible for enrolment in this open-label, randomized controlled trial at 20 centers in China. Patients were randomly assigned 1:1 to CD group (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m 2 ) or CP group (carboplatin AUC 5 plus paclitaxel 175 mg/m 2 ) every 3 weeks for 3-6 cycles. The primary end point was progression free survival (PFS); secondary end points were overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: Between March, 2019 to December, 2021, 395 patients were enrolled, of whom 391 patients were analyzed (195 assigned to CD, 196 to CP). Baseline characteristics were balanced between the two treatment groups. The median follow-up was 21.6 months for the CD group and 22.5 months for the CP group. There was no significant difference in PFS between the two arms (P=0.516); the median PFS was 28.1 months and 30.1 months in the CD and CP arms, respectively. OS data were immature at data cutoff, with a total of 26 deaths in the two treatment groups. In patients with at least one measurable lesion at baseline, ORR was 65.5% in the CD arm and 66.2% in the CP arm (P= 0.941); DCR was 74.1% and 73.8% in the CD and CP arms, respectively (P= 0.971). Among patients who were evaluable by GCIG CA125 criteria, CA125 response was obtained in 86.0% and 88.5% of patients in the CD and CP arms, respectively (P=0.560). More frequent grade 1 to 3 alopecia (32.1% vs 12.3%) and neurotoxicity (20.4% vs 0%) were observed in the CP arm; more hand-foot syndrome (grade 1 to 3, 10.8% vs 2.6%), and oral mucositis (grade 1-3, 12.8% vs 5.1%) in the CD arm. Conclusions: The efficacy of CD regimen is comparable to that of CP, with less alopecia and neurotoxicity. CD may be an alternative first-line treatment for EOC. However, survival data are not yet mature, and longer follow-up is needed. Clinical trial information: NCT03794778 .
Venetoclax pharmacokinetics in subjects with end-stage renal disease undergoing hemodialysis.
Authors: Behnam Noorani, Rajeev Menon, Xin Cen, Kennan Marsh, Weize Huang, Shelly Gupta, Edyta Dobkowska, Thomas Marbury, Ahmed H. Salem
Journal: Journal of Clinical Oncology (2023)

e19042 Background: Venetoclax is a first-in-class Bcl-2 inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia(AML) and is currently being investigated as a treatment for t(11;14)-positive relapsed/refractory multiple myeloma (MM). Renal insufficiency is a common comorbidity in patients with hematologic malignancies, and no clinical study has been conducted to assess how end stage renal disease might affect venetoclax pharmacokinetics. This study aimed to assess the pharmacokinetics of venetoclax after oral administration of a single 100 mg dose of venetoclax in subjects with normal renal function and end-stage renal disease, including those undergoing hemodialysis. Methods: Venetoclax was administered as a single 100 mg dose to 7 healthy female subjects with normal renal function (eGFR &gt; 90 ml/min) and 6 female subjects with end-stage renal disease (ESRD) (eGFR &lt; 15 ml/min) both prior to hemodialysis (Period 1) and between hemodialysis days (Period 2). Intensive PK and protein binding samples were collected from all subjects. Arterial and venous samples were collected from ESRD subjects during hemodialysis to assess the effect of hemodialysis on the pharmacokinetics of venetoclax. Pharmacokinetic parameters were estimated using non-compartmental methods. Results: There was no difference in plasma venetoclax concentrations between arterial and venous samples, suggesting that hemodialysis did not affect the PK of venetoclax. The fraction unbound (f u ) of venetoclax increased approximately 2-fold for subjects with ESRD compared to subjects with normal renal function.The unbound C max and AUC 0-48 of ESRD subjects, between dialysis days were comparable to unbound C max and AUC 0-48 observed in the normal renal function subjects. The harmonic mean t 1/2 between groups (normal renal function vs. ESRD) ranged from 11 and 12.2 hours, demonstrating that end-stage renal disease did not affect the half-life of venetoclax. Conclusions: End-stage renal disease does not alter unbound venetoclax plasma concentrations and no dose adjustment is neededfor patients with renal insufficiency based on pharmacokinetics. Clinical trial information: NCT04810598 .
Intrathecal drug delivery systems for cancer pain control: Insights on current contemporary practices in the US.
Authors: Vasudha Goel, Melissa Ann Geller, Anne Hudson Blaes, Amitabh Gulati
Journal: Journal of Clinical Oncology (2023)

6605 Background: About a third of cancer survivors report moderate to severe pain. Intrathecal drug delivery system (IDDS) is an implantable pain control option for treating intractable chronic pain not responsive to systemic opioid therapy. Studies on the current practices in the US around the utilization of IDDS for cancer pain are lacking. Methods: The Nationwide inpatient sample (NIS) dataset is funded by the Agency for healthcare research and quality (AHRQ) for multistate healthcare research &amp; decision-making. Adult patients admitted to hospitals with a primary or secondary cancer diagnosis between 2016-19 were included. Patients undergoing IDDS implantation were identified using the validated International Classification of Diseases, 10th Revision, Procedure Coding System codes (00HU33Z Insertion of infusion device into spinal canal, percutaneous approach and 0JH80VZ Insertion of infusion pump into abdomen subcutaneous tissue and fascia, open). Baseline demographics, hospital characteristics, and type of cancer associated with IDDS implantation were evaluated in the study. Results: 22,895 patients underwent IDDS surgery amongst 7.06 million hospitalizations from 2016-19. The IDDS cohort consisted of patients in the 65-79 years age group (40.49%), female sex (50.42%), and Caucasian ethnicity (75.82%). Most IDDS surgeries were performed in large, urban teaching hospitals. Conclusions: Despite recommendations supporting IDDS use, a small minority received the treatment with significant racial &amp; socioeconomic disparities in IDDS use. [Table: see text]
Large scale evaluation of pulmonary nodule workup: A real-world study of over 150,000 patients in New York State.
Authors: Vamsidhar Velcheti, Erika Klump, Andrew Long, Hadrian Green, Tessa Williams, Tielman Van Vleck, Hesper Wong, Randall Legg, Jon Apple, Bobby Arelli, Ilker Arslan
Journal: Journal of Clinical Oncology (2023)

8559 Background: Around 1.6 million patients in the US annually have a pulmonary nodule (PN) found on imaging. Previous studies suggest 1-12% of PNs represent an underlying malignancy at a potentially curative stage. PNs ≥6mm are considered higher risk. Despite guideline availability, only about one-third of commercially insured patients with a PN receive recommended workup, which may include further investigation via imaging or surgery. In addition, patients and providers may delay workup of PNs identified during COVID-19. We aimed to describe variations in PN workup for different patient demographic and clinical characteristics at 7 healthcare institutions in New York (NY) state. Methods: We used a retrospective cross-sectional design in which structured demographic and unstructured clinical data were used to analyze patient documents from a NY state health information exchange from January 2018 to February 2022. Clinical features were abstracted using a clinical natural language processing platform, CLiX unlock. Results: 58 million documents from 5.5 million unique patients were analyzed. Of the overall 151,436 patients with PNs, workup was found in 47% (71,071). Across institutions, workup ranged between 24% and 52%; 40% (60,749) had evidence of a PN in the upper lung location. We found 52,789 patients (35%) had a maximum PN ≥6mm and of those, 55% (28,958) had a workup (Table). For patients with a PN ≥6mm, workup for non-English speaking patients was 9% lower than for English speaking patients (47% vs 56%), 17% lower for patients 18-44 years than patients 45-90 years (39% vs 56%), 47% lower for patients presenting with a chest injury rather than cancer screening (28% vs 75%), and 9% higher for patients with initial imaging via chest computed tomography (CT) rather than other CT (58% vs 49%). After the start of the COVID-19 pandemic (January 2020), overall workup decreased 3.8% and prevalence of symptoms such as dyspnea and chest pain increased. Conclusions: The descriptive findings of this analysis demonstrate gaps and variations in workup for patients with PNs across different demographics and clinical scenarios. A subsequent project is underway to explore strategies for improvement in adherence to guideline-recommended care to benefit patients by diagnosing lung cancer at an earlier, potentially curative stage. [Table: see text]